Thalidomide augments maturation and T helper 1-inducing capacity of monocyte-derived dendritic cells in vitro.

IF 2.2 4区 工程技术 Q3 PHARMACOLOGY & PHARMACY
Bioimpacts Pub Date : 2024-12-29 eCollection Date: 2025-01-01 DOI:10.34172/bi.30588
Mohsen Abbaszadeh, Bahar Naseri, Javad Masoumi, Elham Baghbani, Behzad Baradaran, Mohammad Reza Sadeghi
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引用次数: 0

Abstract

Introduction: Dendritic cells (DCs) possess specialized abilities to present antigens and stimulate T cells, making them essential in triggering adaptive immune responses. Thalidomide and its derivatives are classified as a group of medications that possess immunomodulatory properties. Numerous studies have demonstrated the contentious impact of these drugs on DCs. Therefore, the objective of the present study was to assess the influence of Thalidomide therapy on the maturation and stimulation of monocyte-derived DCs, and subsequently examine the consequences of these treated DCs on the immune responses of autologous T cells.

Methods: The immature DCs derived from monocytes were subjected to exposure to Thalidomide and Lipopolysaccharides (LPS) on the fifth day of differentiation, followed by a 24-hour incubation period. On the sixth day, the phenotypic features of the DCs in both the control and treatment groups were assessed using flow cytometry. Subsequently, the gene expression in both the DCs and autologous T cells co-cultured with the DCs was evaluated using the real-time PCR method.

Results: Thalidomide-treated DCs exhibited a significant augmentation in the expression of maturation and stimulatory surface markers CD11c, HLA-DR, and CD86 (P ≤ 0.01), as well as gene expression of TNF-α and IL-12 (P ≤ 0.01) when compared to the control group. Furthermore, co-culture of Thalidomide-treated DCs with T cells increased T-bet and IFN-γ (P ≤ 0.01) expression, while diminished FOXP3 and TGF-β (P ≤ 0.01) expression compared to T cells co-cultured with untreated DCs.

Conclusion: Our findings indicate that in vitro Thalidomide treatment shifts DCs towards an immunogenic state and elevates their T helper 1 inducing capacity, which may be efficient in immunotherapy of various cancers.

沙利度胺增强体外单核细胞来源的树突状细胞的成熟和T辅助1诱导能力。
树突状细胞(dc)具有特异性递呈抗原和刺激T细胞的能力,这使得它们在触发适应性免疫反应中至关重要。沙利度胺及其衍生物被归类为一组具有免疫调节特性的药物。许多研究已经证明了这些药物对dc的有争议的影响。因此,本研究的目的是评估沙利度胺治疗对单核细胞源性树突状细胞成熟和刺激的影响,并随后检查这些处理过的树突状细胞对自体T细胞免疫反应的影响。方法:将单核细胞培养的未成熟dc在分化第5天暴露于沙利度胺和脂多糖(LPS)中,然后进行24小时的孵育。第6天,使用流式细胞术评估对照组和治疗组DCs的表型特征。随后,采用实时荧光定量PCR方法评估dc和与dc共培养的自体T细胞中的基因表达。结果:与对照组相比,沙利度胺处理的树突状细胞成熟和刺激表面标志物CD11c、HLA-DR、CD86的表达显著增加(P≤0.01),TNF-α、IL-12的基因表达显著增加(P≤0.01)。此外,与未处理dc的T细胞共培养相比,沙利度胺处理dc与T细胞共培养提高了T-bet和IFN-γ的表达(P≤0.01),降低了FOXP3和TGF-β的表达(P≤0.01)。结论:体外沙利度胺治疗可使树突状细胞进入免疫原性状态,提高其诱导T -辅助性1的能力,可能在多种癌症的免疫治疗中有效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bioimpacts
Bioimpacts Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
4.80
自引率
7.70%
发文量
36
审稿时长
5 weeks
期刊介绍: BioImpacts (BI) is a peer-reviewed multidisciplinary international journal, covering original research articles, reviews, commentaries, hypotheses, methodologies, and visions/reflections dealing with all aspects of biological and biomedical researches at molecular, cellular, functional and translational dimensions.
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